The major goal of this research proposal is to elucidate the mechanism(s) that regulate the production and circulating concentrations of leptin in humans. Leptin is a newly discovered hormone, produced by the adipose tissue, which is involved in the regulation of metabolism and maintenance of body composition. Obesity is a major disease in the United States affecting one third of the entire population and up to 50% of minority females (African American and Hispanic). A better understanding of the mechanisms that lead to the development of excess adipose tissue will improve the treatment of this disease and associated diseases such as diabetes and hypertension. To accomplish these goals, experiments have been designed to assess the effect of weight loss, weight gain, fasting and feeding on ob gene expression and serum leptin levels. In addition, in vitro experiments utilizing primary adipoyctes isolated from subcutaneous adipose tissue biopsy will be used to assess determine the factors that regulate ob gene expression.